Mechanism of Action Flashcards
What is the mechanism of action of fibrinolytic drugs in STEMI and give two examples of them and when they should be given.
Fibrinolytic drugs such as alteplase (within 6-12hrs) and streptokinase (within 12 hours) inhibit fibrin which degrades the thrombi.
STEMI = complete blockage of coronary artery
Ideally fibrinolytic drugs should be given within 1 hour
How do nitrates work and why can they be used as a prophylaxis treatment for angina too?
(link to symptoms)
Nitrates are vasodilators, they increase blood flow in the coronary artery (flushing symptom) = symptomatic relief of angina.
They also have a vasodilatory effect on the veins which reduces preload and afterload –> which reduces the workload of the heart and oxygen demand. (Hypotensive and headache).
Preload = volume of blood filled in ventricles after diastole
Afterload = Force needed to eject blood
Prophylaxis = Ischemia is where heart issue isn’t receiving enough oxygen so reducing amount of oxygen the heart needs in the first place = less likely to become iscahemic
What is the mechanism of action of Beta-blockers (including B1, B2, and B3 adrenoreceptors)
Beta-blockers are classified as cardioselective and non-cardioselective.
Cardioselective BBs such as bisoprolol, atenolol, and metoprolol inhibit the binding of adrenaline to B1 adrenoreceptors which are predominately located in the heart and are less likely to cause vasoconstriction of the airways.
B2 receptors are located in the bronchial smooth muscles and B3 are located in the adipocytes.
Non-Cardioselective beta-blockers such as propranolol block B1 and B2 equally
Why are cardio selective BBs preferred in diabetic patients?
B2 adrenoreceptors can contribute to hypoglycaemia. Non-cardioselective BBs inhibit B1 and B2 adrenoreceptors equally.
What is the difference in pharmacological properties between lipophilic and hydrophilic BBs?
Lipophilic BBs are cleared hepatically and can cross the BBB to cause sleep disturbances. This includes labetolol, metorpolol, propranolol and carvedilol.
Hydrophilic BB are cleared renally. This includes atenolol and sotalol.
Bisoprolol has mixed properties and does not require any renal or hepatic adjustments
What are the first line treatments in heart failure and what should be added to therapy if symptoms worsen despite optimal treatment (hint 2)
ACEi and BB are first-line treatments - clinical judgement should be used on which medication to start first
An Aldosterone antagonist such as spironolactone or eplerenone unless contraindicated (hyperkalemia or renal impairment)
Hydralazine in combination with a nitrate should be used in patients intolerant to ACE/ARB
Explain the mechanism of action in heart failure for the following:
Aldosterone antagonists
Aldosterone antagonists inhibit the action of aldosterone. This decreases sodium and water retention = decreasing BP and fluid overload
what should be added if there are no improvements with ACE/ARB + BB + MRA in heart failure
Sinus rhythm + BPM 70 + EF <35 = Digoxin
Sinus rhythm + (is not) BPM 70 + EF >35 = ivabradine
EF <35 = Sacubitril valsartan (STOP ace/arb before commencing treatment)
How does ivabradine work?
Ivabradine belongs to the class of drug HCN. It inhibits the channels within the SA node to slow down the heart rate. The SA node acts as the hearts pacemaker. Slowing down the HR allows the heart to pump more blood.
Outline the following for metformin:
Drug class
MOA
SE
Biguanide
Metformin acts on the liver and inhibits gluconeogenesis (carbohydrate to glucose) and it increases insulin sensitivity
First line as it is the strongest insulin sensitizer
S.E –> GI disturbance but can be switched to slow release
Outline the following for Empagliflozin:
Drug class
MOA
SE
SGLT2 Inhibitor
MOA: Inhibit SGLT-2 transport protein which decreases the reabsorption of glucose and increases urinary excretion
S.E - Increased risks of infections due to sugary urine
Ketoacidosis – symptoms are abdominal pain, confusion.
Diabetic ketoacidosis is a life-threatening condition where your body runs of insulin and cannot use glucose for energy and gets the energy from the fat cells. This causes ketones to be released.
Outline the following for Semaglutide:
Drug class
MOA
GLP1 agonist
MOA: Suppresses glucagon release and increases insulin secretion. It also delays gastric emptying which gives the feeling of ‘fullness’
Outline the following for Sitagliptin:
Drug class
MOA
DPP4 inhibitor
MOA – Inhibits DPP4 enzyme which prevents the degradation of GLP-1
Outline the following for Gliclazide
Drug class
MOA
SE
Sulfonylurea – E.g., gliclazide This is also known as the emergency drug except in elderly people
MOA – In type 2 diabetes, there are roughly 20% of beta cells remaining. These drug classes work by essentially squeezing the insulin from the remaining beta cells. Their fast onset of action is why it is given in emergency situations where the pt. has a high HbA1c but it is given for a specific duration.
Not recommended in younger people as we would want to preserve the remaining beta cells.
S.E - Common are weight gain and hyper glycaemia
Outline the following for pioglitazone
Drug class
MOA
SE
MOA: reducing insulin resistance and increasing the sensitivity of body cells to insulin
This is the second strongest insulin sensitizer after metformin. It is usually issued in males and is not recommended in women of menopausal age; elderly people are people at risk of fractures.
S.E - Increased risk of fractures
